Objective:

In utero and early life experiences affect physiological development and can influence sensitivity to environmental factors throughout life. In this project, we explored the interplay between certain early life events, characterizations of air pollutant mixtures developed as part of the Center’s Mixtures Characterization Toolkit, and a range of pediatric health outcomes using two large, population-based birth cohorts. One cohort consisted of roughly 1.7 million Georgia birth records that had been geocoded to the Census block level and linked with pediatric emergency department visits by staff at the Georgia Department of Human Resources. Using this statewide birth cohort, we investigated acute effects of air pollution mixtures on respiratory health outcomes and ear infections in children, and we assessed whether children who were born premature or low birth weight were more sensitive to ambient air pollutant concentrations than their counterparts. Further, we used the statewide birth cohort to investigate whether ambient air pollutant mixtures during pregnancy were associated with the risk of preterm delivery or reduced birth weight. The second birth cohort was comprised of children who were members of the Kaiser Permanente Georgia Health Maintenance Organization in metropolitan Atlanta. In this birth cohort, where comprehensive medical and residential histories were available for each study subject, we examined whether air pollutant mixtures during the first year of life were associated with the incidence of childhood asthma. We used these two birth cohorts to address the Project 3 specific objectives:

Specific Objective 1. Characterize the multipollutant atmosphere using five complementary approaches from the Mixtures Characterization Toolkit:

Asthma in children age 5 years and older andinvestigate whether these relationships are modified by gestational age or birth weight.

Specific Objective 3. Use the statewide birth cohort to investigate relationships between ambient air pollutant mixtures during pregnancy and risk of preterm delivery and reduced birth weight.

Specific Objective 4. Use the Kaiser Permanente birth cohort to investigate longer-term relationships between ambient air pollutant mixtures during pregnancy and the first year of life and incident asthma in childhood.

Specific Objective 5. Use the Kaiser Permanente birth cohort to describe residential mobility during pregnancy and implications for exposure estimation.

Summary/Accomplishments (Outputs/Outcomes):

In Project 3, we used a variety of complementary air quality characterizations and statistical approaches to estimate associations of ambient air pollutant mixtures on child health. Together, these findings highlight the important role of ambient air pollutants in the exacerbation of several common pediatric diseases. Most prominently, our epidemiologic analyses show associations for both ozone and PM2.5 on pediatric asthma exacerbations. These conclusions are strengthened by the consistency of findings across a variety of air quality models and statistical analyses. For example, we observed associations with ozone and PM2.5 in time series models using measured concentrations in Atlanta (Strickland et al., 2014; Darrow et al., 2014); similar findings were obtained when we used joint effects models (Winquist et al., 2014), classification and regression trees (Gass et al., 2014) and self-organizing maps (Pearce et al., 2015) to better characterize air quality mixtures. Through this work, we reported that associations between short-term changes in several pollutant concentrations (including both ozone and PM2.5) and pediatric asthma emergency visits tended to be of greater magnitude for children born premature and for children born to African American mothers (Strickland et al., 2014).

Pediatric outcomes other than asthma were also investigated. For example, in Xiao et al. (2016) bronchiolitis, pneumonia, bronchitis, otitis media, and upper respiratory infection were associated with short-term changes in several ambient air pollutant concentrations estimated using the observation-fused CMAQ models, including PM2.5 components such as elemental carbon and organic carbon. The satellite-based models of PM2.5, however, only showed associations for asthma and upper respiratory infection; the associations for the other outcome groups in this study were null (Strickland et al., 2016).

Statewide analyses of air pollution concentrations and pregnancy outcomes were investigated in Hao et al. (2016) and Keller et al. (2017). Hao et al. (2016) estimated associations of preterm birth with trimester-long and total pregnancy average concentrations of 11 pollutants estimated using the observation-fused CMAQ models. Associations were observed for several gaseous pollutants and for PM2.5, although the ozone associations were null. Stratification by potentially susceptible subgroups showed associations tended to be of stronger magnitude for births to African American mothers, mothers in large metropolitan counties, and mothers with less than high school education. In Keller et al. (2017), we observed associations between third-trimester PM2.5 concentrations and birth weight after performing measurement error correction for the spatial incompatibility between the locations of the air quality monitors and the birth locations. This project was part of a collaborative study between Emory University and University of Washington. As work in progress, we are finalizing a quantile regression analysis of the association between air pollutant concentrations and birth weight to investigate whether the magnitude of the association differs for various quantiles of the birth weight distribution.

Using Kaiser Permanente data, we investigated associations of early life exposure to PM2.5 from traffic and development of asthma. An RLINE dispersion model at 250 meter resolution (Zhai et al., 2016) and an RLine + CMAQ fusion model at 250 meter resolution (Bates et al., in progress) were created to estimate near-roadway pollutant impacts at fine spatial scale. Epidemiologic analysis using the RLine dispersion model showed increases in cumulative incidence of asthma among children over several age intervals (Pennington et al., work in progress). In this study, we also estimated the potential impact of exposure misclassification due to maternal mobility during pregnancy on association estimates and found biases of between -2% and -10% (Pennington et al., 2016a). We also examined the predictive ability of various early life definitions of asthma as markers of subsequent asthma (Pennington et al., 2016b).

Conclusions:

Our analyses of short-term changes in pollutant concentrations in relation to pediatric respiratory events support the conclusion that several different pollutants are associated with these diseases. Various approaches to characterize pollutant mixtures, including joint effects modeling, classification and regression trees, source apportionment, and self-organizing maps, were implemented to investigate the health effects of pollutant mixtures. Broadly, we did not observe consistent evidence for positive synergism among pollutants across our studies. More evidence was found to support effect modification of pollutant associations by susceptibility factors such as preterm birth, maternal race, and maternal education (Strickland et al., 2014; Hao et al., 2016). Future work will help to inform the validity of these potentially important susceptibility factors. Our analyses of early life traffic exposures and incident asthma in a racially diverse population provide evidence to further support previous literature on this association. Through this work, we have developed an innovative modeling approach to fuse chemical transport model results with dispersion model estimates to better estimate near-roadway impacts, and we found that exposure misclassification due to maternal mobility during pregnancy is not likely to cause a large bias in the effect estimates.

Main Center Abstract and Reports:

Subprojects under this Center:(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).R834799C001 Development and Deployment of an Instrumentation Suite for Comprehensive Air Quality Characterization Including Aerosol ROSR834799C002 Examining In-Vehicle Pollution and Oxidative Stress in a Cohort of Daily CommutersR834799C003 Novel Estimates of Pollutant Mixtures and Pediatric Health in Two Birth CohortsR834799C004 A Multi-City Time-Series Study of Pollutant Mixtures and Acute Morbidity

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.